This study proposes to use a new cytogenetic method, comparative genomic hybridization (CGH), to identify novel genetic alterations in oral cavity squamous cell tumors. In comparative genomic hybridization, chromosomal DNA from tumors is uniformly labelled with a green fluorochrome and normal DNA is labelled with a red fluorochrome. The labelled DNAs are then simultaneously hybridized to normal human metaphase spreads. Quantitation of the green to red fluorescence ratio along the length of each chromosome allows regions of increased or decreased copy number to be identified and mapped in a single experiment. The method has been used successfully to identify novel aneuploidies, amplifications and deletions as small as several megabases. Fifty specimens of oral cavity tumors will be examined by CGH in order to identify all cytogenetic alterations that may contribute to tumorigenesis in this tumor type. Preliminary data indicate that CGH can be successfully performed on DNA extracted from fixed, paraffin-embedded tumor tissue and from fresh tumor specimens from a variety of tumors including oral cavity tumors and lung tumors. Alterations identified by CGH will be correlated with efficacy of radiotherapy as defined by efficiency of local control of tumor growth. In addition, novel alterations could become candidates for future positional cloning efforts designed to determine the molecular function of the gene(s) involved.